{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T18:21:19Z","timestamp":1788891679582,"version":"build-2803163510"},"reference-count":36,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,12,7]],"date-time":"2020-12-07T00:00:00Z","timestamp":1607299200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Laboratory Analysis"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Drug resistance is a common phenomenon frequently observed in countries where leishmaniasis is endemic. Due to the production of the pteridine reductase enzyme (PTR1), drugs lose their efficacy, and consequently, the patient becomes unresponsive to treatment. This study aimed to compare the in vitro effect of meglumine antimoniate (MA) on non\u2010 healing <jats:italic>Leishmania tropica<\/jats:italic> isolates and on MA transfected non\u2010healing one to PTR1.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Two non\u2010healing and one healing isolates of <jats:italic>L. tropica<\/jats:italic> were collected from patients who received two courses or one cycle of intralesional MA along with biweekly liquid nitrogen cryotherapy or systemic treatment alone, respectively. After confirmation of <jats:italic>L. tropica<\/jats:italic> isolates by polymerase chain reaction (PCR), the recombinant plasmid pcDNA\u2010rPTR (antisense) was transfected via electroporation and cultured on M199. Isolates in form of promastigotes were treated with different concentrations of MA and read using an enzyme\u2010linked immunosorbent assay (ELISA) reader and the half inhibitory concentration (IC<jats:sub>50<\/jats:sub>) value was calculated. The amastigotes were grown in mouse macrophages and were similarly treated with various concentrations of MA. The culture glass slides were stained, and the mean number of intramacrophage amastigotes and infected macrophages were assessed in triplicate for both stages.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>All three transfected isolates displayed a reduction in optical density compared with the promastigotes in respective isolates, although there was no significant difference between non\u2010healing and healing isolates. In contrast, in the clinical form (amastigotes), there was a significant difference between non\u2010healing and healing isolates (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The results indicated that the PTR1 gene reduced the efficacy of the drug, and its inhibition by antisense and could improve the treatment of non\u2010healing cases. These findings have future implications in the prophylactic and therapeutic modality of non\u2010 healing <jats:italic>Leishmania<\/jats:italic> isolates to drug.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcla.23670","type":"journal-article","created":{"date-parts":[[2020,12,7]],"date-time":"2020-12-07T09:51:21Z","timestamp":1607334681000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The potential therapeutic role of PTR1 gene in non\u2010healing anthroponotic cutaneous leishmaniasis due to <i>Leishmania tropica<\/i>"],"prefix":"10.1002","volume":"35","author":[{"given":"Monireh","family":"Sezavar","sequence":"first","affiliation":[{"name":"Department of Experimental Sciences Faculty of Allied medicine Alborz University of Medical Sciences Karaj Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iraj","family":"Sharifi","sequence":"additional","affiliation":[{"name":"Leishmaniasis Research Centre 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